{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T03:13:47Z","timestamp":1790392427970,"version":"4.1.0"},"reference-count":73,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2021,7,21]],"date-time":"2021-07-21T00:00:00Z","timestamp":1626825600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"GRAL"},{"name":"Chemistry Biology Health [CBH] Graduate School of University Grenoble Alpes","award":["ANR-10-LABX-49-01"],"award-info":[{"award-number":["ANR-10-LABX-49-01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,2,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background and Aims<\/jats:title>\n                  <jats:p>Inflammatory bowel diseases are highly debilitating conditions that require constant monitoring and life-long medication. Current treatments are focused on systemic administration of immunomodulatory drugs, but they have a broad range of undesirable side-effects. RNA interference is a highly specific endogenous mechanism that regulates the expression of the gene at the transcript level, which can be repurposed using exogenous short interfering RNA [siRNA] to repress expression of the target gene. While siRNA therapeutics can offer an alternative to existing therapies, with a high specificity critical for chronically administrated drugs, evidence of their potency compared to chemical kinase inhibitors used in clinics is still lacking in alleviating an adverse inflammatory response.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We provide a framework to select highly specific siRNA, with a focus on two kinases strongly involved in pro-inflammatory diseases, namely JAK1 and JAK3. Using western-blot, real-time quantitative PCR and large-scale analysis, we assessed the specificity profile of these siRNA drugs and compared their efficacy to the most recent and promising kinase inhibitors for Janus kinases [Jakinibs], tofacitinib and filgotinib.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>siRNA drugs can reach higher efficiency and selectivity at lower doses [5 pM vs 1 \u00b5M] than Jakinibs. Moreover, JAK silencing lasted up to 11 days, even with 6 h pulse transfection.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The siRNA-based drugs developed hold the potential to develop more potent therapeutics for chronic inflammatory diseases.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ecco-jcc\/jjab129","type":"journal-article","created":{"date-parts":[[2021,7,20]],"date-time":"2021-07-20T19:33:33Z","timestamp":1626809613000},"page":"286-300","source":"Crossref","is-referenced-by-count":14,"title":["Therapeutic siRNAs Targeting the JAK\/STAT Signalling Pathway in Inflammatory Bowel Diseases"],"prefix":"10.1093","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0312-8320","authenticated-orcid":false,"given":"Flora","family":"Cl\u00e9ment","sequence":"first","affiliation":[{"name":"Univ. Grenoble Alpes, CEA, INSERM, IRIG, Biomics, Grenoble, France"},{"name":"Univ. Grenoble Alpes, INSERM U1209, CNRS UMR5309, IAB, La Tronche, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrien","family":"Nougar\u00e8de","sequence":"additional","affiliation":[{"name":"Univ. Grenoble Alpes, CEA, Leti, Division for Biology and Healthcare Technologies, Microfluidic Systems and Bioengineering Lab, Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phanie","family":"Combe","sequence":"additional","affiliation":[{"name":"Univ. Grenoble Alpes, CEA, INSERM, IRIG, Biomics, Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9rique","family":"Kermarrec","sequence":"additional","affiliation":[{"name":"Univ. Grenoble Alpes, CEA, INSERM, IRIG, Biomics, Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arindam K","family":"Dey","sequence":"additional","affiliation":[{"name":"Univ. Grenoble Alpes, INSERM U1209, CNRS UMR5309, IAB, La Tronche, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Obeid","sequence":"additional","affiliation":[{"name":"Univ. Grenoble Alpes, CEA, INSERM, IRIG, Biomics, Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnaud","family":"Millet","sequence":"additional","affiliation":[{"name":"Univ. Grenoble Alpes, Inserm U1209, CNRS UMR5309, Team Mechanobiology, immunity and Cancer, Institute for Advanced Biosciences, La Tronche, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrice P","family":"Navarro","sequence":"additional","affiliation":[{"name":"Univ. Grenoble Alpes, CEA, Leti, Division for Biology and Healthcare Technologies, Microfluidic Systems and Bioengineering Lab, Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrice N","family":"Marche","sequence":"additional","affiliation":[{"name":"Univ. Grenoble Alpes, INSERM U1209, CNRS UMR5309, IAB, La Tronche, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Sulpice","sequence":"additional","affiliation":[{"name":"Univ. Grenoble Alpes, CEA, INSERM, IRIG, Biomics, Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Gidrol","sequence":"additional","affiliation":[{"name":"Univ. Grenoble Alpes, CEA, INSERM, IRIG, Biomics, Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,7,21]]},"reference":[{"key":"2022022311192480300_CIT0001","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/cei.13101","article-title":"Genetics of immune-mediated inflammatory diseases","volume":"193","author":"David","year":"2018","journal-title":"Clin Exp Immunol"},{"key":"2022022311192480300_CIT0002","doi-asserted-by":"crossref","first-page":"198","DOI":"10.12788\/j.sder.2018.041","article-title":"JAK-STAT signaling pathway inhibition: a role for treatment of various dermatologic diseases","volume":"37","author":"Kahn","year":"2018","journal-title":"Semin Cutan Med Surg"},{"key":"2022022311192480300_CIT0003","article-title":"Targeting JAK-STAT","author":"Luo","year":"2020","journal-title":"Trends Pharmacol Sci"},{"key":"2022022311192480300_CIT0004","doi-asserted-by":"crossref","first-page":"2623","DOI":"10.4049\/jimmunol.178.5.2623","article-title":"The JAK-STAT signaling pathway: input and output integration","volume":"178","author":"Murray","year":"2007","journal-title":"J Immunol"},{"key":"2022022311192480300_CIT0005","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1161\/01.RES.85.10.884","article-title":"Characterization of insulin-like growth factor-1-induced activation of the JAK\/STAT pathway in rat cardiomyocytes","volume":"85","author":"Takahashi","year":"1999","journal-title":"Circ Res"},{"key":"2022022311192480300_CIT0006","doi-asserted-by":"crossref","first-page":"5023","DOI":"10.1021\/jm401490p","article-title":"Discovery and development of Janus kinase (JAK) inhibitors for inflammatory diseases","volume":"57","author":"Clark","year":"2014","journal-title":"J Med Chem"},{"key":"2022022311192480300_CIT0007","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.coph.2020.10.010","article-title":"JAK inhibitors: current position in treatment strategies for use in inflammatory bowel disease","volume":"55","author":"Hernandez-Rocha","year":"2020","journal-title":"Curr Opin Pharmacol"},{"key":"2022022311192480300_CIT0008","doi-asserted-by":"crossref","DOI":"10.1016\/j.cgh.2020.10.038","article-title":"Efficacy and safety of extended induction with tofacitinib for the treatment of ulcerative colitis","author":"Sandborn","year":"2020","journal-title":"Clin Gastroenterol Hepatol."},{"key":"2022022311192480300_CIT0009","doi-asserted-by":"crossref","first-page":"1987","DOI":"10.1007\/s40265-020-01439-0","article-title":"Filgotinib: first approval","volume":"80","author":"Dhillon","year":"2020","journal-title":"Drugs"},{"key":"2022022311192480300_CIT0010","author":"Galapagos","year":"2016"},{"key":"2022022311192480300_CIT0011","doi-asserted-by":"crossref","first-page":"i4","DOI":"10.1093\/rheumatology\/key432","article-title":"Janus kinases to jakinibs: from basic insights to clinical practice","volume":"58","author":"Gadina","year":"2019","journal-title":"Rheumatology (Oxford)"},{"key":"2022022311192480300_CIT0012","doi-asserted-by":"crossref","first-page":"101606","DOI":"10.1016\/j.bpg.2019.03.002","article-title":"Pharmacology, efficacy and safety of JAK inhibitors in Crohn\u2019s disease","volume":"38-39","author":"Ma","year":"2019","journal-title":"Best Pract Res Clin Gastroenterol"},{"key":"2022022311192480300_CIT0013","article-title":"Maintenance of remission with tofacitinib therapy in patients with ulcerative colitis","author":"Colombel","year":"2020","journal-title":"Clin Gastroenterol Hepatol"},{"key":"2022022311192480300_CIT0014","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1038\/35888","article-title":"Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans","volume":"391","author":"Fire","year":"1998","journal-title":"Nature"},{"key":"2022022311192480300_CIT0015","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1038\/s41573-019-0017-4","article-title":"The current state and future directions of RNAi-based therapeutics","volume":"18","author":"Setten","year":"2019","journal-title":"Nat Rev Drug Discov"},{"key":"2022022311192480300_CIT0016","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1056\/NEJMoa1716153","article-title":"Patisiran, an RNAi therapeutic, for hereditary transthyretin amyloidosis","volume":"379","author":"Adams","year":"2018","journal-title":"N Engl J Med"},{"key":"2022022311192480300_CIT0017","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1038\/s41587-020-0494-3","article-title":"Second RNAi drug approved","volume":"38","year":"2020","journal-title":"Nat Biotechnol"},{"key":"2022022311192480300_CIT0018","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/nrd3010","article-title":"Recognizing and avoiding siRNA off-target effects for target identification and therapeutic application","volume":"9","author":"Jackson","year":"2010","journal-title":"Nat Rev Drug Discov"},{"key":"2022022311192480300_CIT0019","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.biomaterials.2019.04.018","article-title":"3D type I collagen environment leads up to a reassessment of the classification of human macrophage polarizations","volume":"208","author":"Court","year":"2019","journal-title":"Biomaterials"},{"key":"2022022311192480300_CIT0020","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1186\/1471-2105-7-520","article-title":"An accurate and interpretable model for siRNA efficacy prediction","volume":"7","author":"Vert","year":"2006","journal-title":"BMC Bioinformatics"},{"key":"2022022311192480300_CIT0021","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-1-62703-119-6_1","article-title":"What parameters to consider and which software tools to use for target selection and molecular design of small interfering RNAs","volume":"942","author":"Matveeva","year":"2013","journal-title":"Methods Mol Biol"},{"key":"2022022311192480300_CIT0022","doi-asserted-by":"crossref","first-page":"pdb.top097436","DOI":"10.1101\/pdb.top097436","article-title":"RNA interference and small RNA analysis","volume":"2019","author":"Li","year":"2019","journal-title":"Cold Spring Harb Protoc"},{"key":"2022022311192480300_CIT0023","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1038\/nbt831","article-title":"Expression profiling reveals off-target gene regulation by RNAi","volume":"21","author":"Jackson","year":"2003","journal-title":"Nat Biotechnol"},{"key":"2022022311192480300_CIT0024","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1261\/rna.25706","article-title":"Widespread siRNA \u201coff-target\u201d transcript silencing mediated by seed region sequence complementarity","volume":"12","author":"Jackson","year":"2006","journal-title":"RNA"},{"key":"2022022311192480300_CIT0025","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1261\/rna.1326809","article-title":"MicroRNA-like off-target transcript regulation by siRNAs is species specific","volume":"15","author":"Burchard","year":"2009","journal-title":"RNA"},{"key":"2022022311192480300_CIT0026","doi-asserted-by":"crossref","first-page":"e63","DOI":"10.1093\/nar\/gkm088","article-title":"Comparison of approaches for rational siRNA design leading to a new efficient and transparent method","volume":"35","author":"Matveeva","year":"2007","journal-title":"Nucleic Acids Res"},{"key":"2022022311192480300_CIT0027","doi-asserted-by":"crossref","first-page":"5250","DOI":"10.3390\/ijms21155250","article-title":"Modulating the crosstalk between the tumor and its microenvironment using RNA interference: a treatment strategy for hepatocellular carcinoma","volume":"21","author":"Mroweh","year":"2020","journal-title":"Int J Mol Sci"},{"key":"2022022311192480300_CIT0028","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1007\/978-1-61779-439-1_9","article-title":"Control of the interferon response in RNAi experiments","volume":"820","author":"Nejepinska","year":"2012","journal-title":"Methods Mol Biol"},{"key":"2022022311192480300_CIT0029","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1093\/intimm\/12.11.1499","article-title":"Characterization of IL-4 and IL-13 signals dependent on the human IL-13 receptor alpha chain 1: redundancy of requirement of tyrosine residue for STAT3 activation","volume":"12","author":"Umeshita-Suyama","year":"2000","journal-title":"Int Immunol"},{"key":"2022022311192480300_CIT0030","first-page":"e27638","article-title":"IL-4, JAK-STAT signaling, and pain","volume":"2","author":"Busch-Dienstfertig","year":"2013","journal-title":"JAKSTAT"},{"key":"2022022311192480300_CIT0031","doi-asserted-by":"crossref","first-page":"10212","DOI":"10.1074\/jbc.275.14.10212","article-title":"Interleukin-4 mediates cell growth inhibition through activation of Stat1","volume":"275","author":"Chang","year":"2000","journal-title":"J Biol Chem"},{"key":"2022022311192480300_CIT0032","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1046\/j.1432-1327.1999.00719.x","article-title":"Different protein turnover of interleukin-6-type cytokine signalling components","volume":"265","author":"Siewert","year":"1999","journal-title":"Eur J Biochem"},{"key":"2022022311192480300_CIT0033","doi-asserted-by":"crossref","first-page":"2068","DOI":"10.1038\/nprot.2007.278","article-title":"A protocol for designing siRNAs with high functionality and specificity","volume":"2","author":"Birmingham","year":"2007","journal-title":"Nat Protoc"},{"key":"2022022311192480300_CIT0034","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1093\/ecco-jcc\/jjz186","article-title":"Efficacy of JAK inhibitors in Crohn\u2019s Disease","volume":"14","author":"Rogler","year":"2020","journal-title":"J Crohns Colitis"},{"key":"2022022311192480300_CIT0035","author":"Pfizer","year":"2021"},{"key":"2022022311192480300_CIT0036","author":"Gilead Sciences","year":"2021"},{"key":"2022022311192480300_CIT0037","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1002\/JLB.5RI0218-084R","article-title":"Translational and clinical advances in JAK-STAT biology: the present and future of jakinibs","volume":"104","author":"Gadina","year":"2018","journal-title":"J Leukoc Biol"},{"key":"2022022311192480300_CIT0038","doi-asserted-by":"crossref","first-page":"e0207558","DOI":"10.1371\/journal.pone.0207558","article-title":"STAT6 knockdown using multiple siRNA sequences inhibits proliferation and induces apoptosis of human colorectal and breast cancer cell lines","volume":"14","author":"Salguero-Aranda","year":"2019","journal-title":"PLoS One"},{"key":"2022022311192480300_CIT0039","doi-asserted-by":"crossref","first-page":"2461","DOI":"10.1056\/NEJMoa1407250","article-title":"Mongersen, an oral SMAD7 antisense oligonucleotide, and Crohn\u2019s disease","volume":"372","author":"Monteleone","year":"2015","journal-title":"N Engl J Med"},{"key":"2022022311192480300_CIT0040","doi-asserted-by":"crossref","first-page":"687","DOI":"10.14309\/ajg.0000000000000564","article-title":"Mongersen and SMAD-7 inhibition, not a lucky 7 for patients with IBD: when trial design is as important as disease therapy","volume":"115","author":"Bewtra","year":"2020","journal-title":"Am J Gastroenterol"},{"key":"2022022311192480300_CIT0041","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1038\/nmat2859","article-title":"Orally delivered thioketal nanoparticles loaded with TNF-\u03b1-siRNA target inflammation and inhibit gene expression in the intestines","volume":"9","author":"Wilson","year":"2010","journal-title":"Nat Mater"},{"key":"2022022311192480300_CIT0042","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.jconrel.2015.12.021","article-title":"Colonic gene silencing using siRNA-loaded calcium phosphate\/PLGA nanoparticles ameliorates intestinal inflammation in vivo","volume":"222","author":"Frede","year":"2016","journal-title":"J Control Release"},{"key":"2022022311192480300_CIT0043","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1038\/mt.2013.214","article-title":"Targeting intestinal inflammation with CD98 siRNA\/PEI-loaded nanoparticles","volume":"22","author":"Laroui","year":"2014","journal-title":"Mol Ther"},{"key":"2022022311192480300_CIT0044","doi-asserted-by":"crossref","first-page":"2603","DOI":"10.1056\/NEJMoa2034577","article-title":"Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine","volume":"383","author":"Polack","year":"2020","journal-title":"N Engl J Med"},{"key":"2022022311192480300_CIT0045","first-page":"NEJMoa2035389","article-title":"Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine","author":"Baden","year":"2020","journal-title":"N Engl J Med"},{"key":"2022022311192480300_CIT0046","doi-asserted-by":"crossref","first-page":"2178","DOI":"10.1038\/s41598-018-20632-6","article-title":"Oral delivery of siRNA lipid nanoparticles: fate in the GI tract","volume":"8","author":"Ball","year":"2018","journal-title":"Sci Rep"},{"key":"2022022311192480300_CIT0047","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1007\/s11427-018-9438-y","article-title":"siRNA therapeutics: a clinical reality","volume":"63","author":"Saw","year":"2020","journal-title":"Sci China Life Sci"},{"key":"2022022311192480300_CIT0048","doi-asserted-by":"crossref","first-page":"3507","DOI":"10.1073\/pnas.1222878110","article-title":"Genomic responses in mouse models poorly mimic human inflammatory diseases","volume":"110","author":"Seok","year":"2013","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2022022311192480300_CIT0049","doi-asserted-by":"crossref","first-page":"e70","DOI":"10.1093\/nar\/gky030","article-title":"Direct transfection of clonal organoids in Matrigel microbeads: a promising approach toward organoid-based genetic screens","volume":"46","author":"Laperrousaz","year":"2018","journal-title":"Nucleic Acids Res"},{"key":"2022022311192480300_CIT0050","doi-asserted-by":"crossref","first-page":"3109","DOI":"10.1158\/1078-0432.CCR-16-1508","article-title":"Malignant astrocytic tumor progression potentiated by JAK-mediated recruitment of myeloid cells","volume":"23","author":"Rajappa","year":"2017","journal-title":"Clin Cancer Res"},{"key":"2022022311192480300_CIT0051","doi-asserted-by":"crossref","first-page":"571","DOI":"10.2174\/1568009618666181016165604","article-title":"Targeting upstream kinases of STAT3 in human medulloblastoma cells","volume":"19","author":"Wei","year":"2019","journal-title":"Curr Cancer Drug Targets"},{"key":"2022022311192480300_CIT0052","doi-asserted-by":"crossref","first-page":"143997","DOI":"10.1016\/j.gene.2019.143997","article-title":"Akt1 and Jak1 siRNA based silencing effects on the proliferation and apoptosis in head and neck squamous cell carcinoma","volume":"714","author":"Vakili Saatloo","year":"2019","journal-title":"Gene"},{"key":"2022022311192480300_CIT0053","doi-asserted-by":"crossref","first-page":"3191","DOI":"10.3892\/ol.2017.5861","article-title":"Jak3 is involved in CCR7-dependent migration and invasion in metastatic squamous cell carcinoma of the head and neck","volume":"13","author":"Zhang","year":"2017","journal-title":"Oncol Lett"},{"key":"2022022311192480300_CIT0054","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1007\/s12094-012-0774-6","article-title":"JAK\/STAT signal pathway activation promotes progression and survival of human oesophageal squamous cell carcinoma","volume":"14","author":"You","year":"2012","journal-title":"Clin Transl Oncol"},{"key":"2022022311192480300_CIT0055","first-page":"11828","article-title":"MicroRNA-30b targets CBX3 and regulates cell proliferation, apoptosis, and migration in esophageal squamous cell carcinoma via the JAK2\/STAT3 signaling pathway","volume":"10","author":"Meng","year":"2017","journal-title":"Int J Clin Exp Pathol"},{"key":"2022022311192480300_CIT0056","doi-asserted-by":"crossref","first-page":"2192","DOI":"10.1016\/j.celrep.2018.10.063","article-title":"Janus kinase 1 plays a critical role in mammary cancer progression","volume":"25","author":"Wehde","year":"2018","journal-title":"Cell Rep"},{"key":"2022022311192480300_CIT0057","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1016\/j.jmb.2011.03.017","article-title":"Cell invasion of highly metastatic MTLn3 cancer cells is dependent on phospholipase D2 (PLD2) and Janus kinase 3 (JAK3)","volume":"408","author":"Henkels","year":"2011","journal-title":"J Mol Biol"},{"key":"2022022311192480300_CIT0058","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.canlet.2017.06.016","article-title":"Anti-myeloma effects of ruxolitinib combined with bortezomib and lenalidomide: a rationale for JAK\/STAT pathway inhibition in myeloma patients","volume":"403","author":"de Oliveira","year":"2017","journal-title":"Cancer Lett"},{"key":"2022022311192480300_CIT0059","first-page":"1442","article-title":"AT-9283, a small-molecule multi-targeted kinase inhibitor for the potential treatment of cancer","volume":"11","author":"Kimura","year":"2010","journal-title":"Curr Opin Investig Drugs"},{"key":"2022022311192480300_CIT0060","first-page":"159","article-title":"Association analyses of the JAK\/STAT signaling pathway with the progression and prognosis of colon cancer","volume":"17","author":"Tang","year":"2019","journal-title":"Oncol Lett"},{"key":"2022022311192480300_CIT0061","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1016\/S0002-9440(10)61187-X","article-title":"Constitutive activation of JAK3\/STAT3 in colon carcinoma tumors and cell lines: inhibition of JAK3\/STAT3 signaling induces apoptosis and cell cycle arrest of colon carcinoma cells","volume":"167","author":"Lin","year":"2005","journal-title":"Am J Pathol"},{"key":"2022022311192480300_CIT0062","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/s10020-019-0111-4","article-title":"PRSS1 mutation: a possible pathomechanism of pancreatic carcinogenesis and pancreatic cancer","volume":"25","author":"Liu","year":"2019","journal-title":"Mol Med"},{"key":"2022022311192480300_CIT0063","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1158\/1541-7786.MCR-16-0337","article-title":"Potent EMT and CSC phenotypes are induced by oncostatin-M in pancreatic cancer","volume":"15","author":"Smigiel","year":"2017","journal-title":"Mol Cancer Res"},{"key":"2022022311192480300_CIT0064","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.17219\/acem\/104543","article-title":"Targeted blockade of interleukin 9 inhibits tumor growth in murine model of pancreatic cancer","volume":"28","author":"Lu","year":"2019","journal-title":"Adv Clin Exp Med"},{"key":"2022022311192480300_CIT0065","doi-asserted-by":"crossref","first-page":"3324","DOI":"10.1172\/JCI126022","article-title":"IL-6\/JAK1 pathway drives PD-L1 Y112 phosphorylation to promote cancer immune evasion","volume":"129","author":"Chan","year":"2019","journal-title":"J Clin Invest"},{"key":"2022022311192480300_CIT0066","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1586\/era.10.203","article-title":"JAK3 pathway is constitutively active in B-lineage acute lymphoblastic leukemia","volume":"11","author":"Uckun","year":"2011","journal-title":"Expert Rev Anticancer Ther"},{"key":"2022022311192480300_CIT0067","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1038\/s41375-017-0004-x","article-title":"Oncogenic activation of JAK3-STAT signaling confers clinical sensitivity to PRN371, a novel selective and potent JAK3 inhibitor, in natural killer\/T-cell lymphoma","volume":"32","author":"Nairism\u00e4gi","year":"2018","journal-title":"Leukemia"},{"key":"2022022311192480300_CIT0068","doi-asserted-by":"crossref","first-page":"327","DOI":"10.2174\/138945006776054997","article-title":"Targeting JAK3 and BTK tyrosine kinases with rationally-designed inhibitors","volume":"7","author":"Vassilev","year":"2006","journal-title":"Curr Drug Targets"},{"key":"2022022311192480300_CIT0069","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1080\/19382014.2019.1650580","article-title":"JAK3 inhibitor-based immunosuppression in allogeneic islet transplantation in cynomolgus monkeys","volume":"11","author":"Kim","year":"2019","journal-title":"Islets"},{"key":"2022022311192480300_CIT0070","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.phrs.2013.06.007","article-title":"Involvement of JAK\/STAT signaling in the pathogenesis of inflammatory bowel disease","volume":"76","author":"Coskun","year":"2013","journal-title":"Pharmacol Res"},{"key":"2022022311192480300_CIT0071","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1007\/s40265-017-0701-9","article-title":"JAK-STAT signaling as a target for inflammatory and autoimmune diseases: current and future prospects","volume":"77","author":"Banerjee","year":"2017","journal-title":"Drugs"},{"key":"2022022311192480300_CIT0072","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.cytogfr.2020.06.013","article-title":"The potential of JAK\/STAT pathway inhibition by ruxolitinib in the treatment of COVID-19","volume":"54","author":"Goker Bagca","year":"2020","journal-title":"Cytokine Growth Factor Rev"},{"key":"2022022311192480300_CIT0073","doi-asserted-by":"crossref","first-page":"eabe4724","DOI":"10.1126\/sciadv.abe4724","article-title":"JAK inhibition reduces SARS-CoV-2 liver infectivity and modulates inflammatory responses to reduce morbidity and mortality","volume":"7","author":"Stebbing","year":"2021","journal-title":"Sci Adv"}],"container-title":["Journal of Crohn's and Colitis"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/ecco-jcc\/advance-article-pdf\/doi\/10.1093\/ecco-jcc\/jjab129\/39200702\/jjab129.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ecco-jcc\/article-pdf\/16\/2\/286\/42581124\/jjab129.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ecco-jcc\/article-pdf\/16\/2\/286\/42581124\/jjab129.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,23]],"date-time":"2022-02-23T13:47:21Z","timestamp":1645624041000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ecco-jcc\/article\/16\/2\/286\/6324882"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,21]]},"references-count":73,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,7,21]]},"published-print":{"date-parts":[[2022,2,23]]}},"URL":"https:\/\/doi.org\/10.1093\/ecco-jcc\/jjab129","relation":{},"ISSN":["1873-9946","1876-4479"],"issn-type":[{"value":"1873-9946","type":"print"},{"value":"1876-4479","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,2,1]]},"published":{"date-parts":[[2021,7,21]]}}}